The platinum-based anticancer drugs, including cisplatin and carboplatin, are among the most potent and widely used chemotherapeutic agents. They alone or in combination with other drugs are the standard of care for treating a variety of cancers, including testicular, ovarian, colorectal, bladder, lung, and head and neck cancers (Wang and Lippard, 2005). The major limitations for the clinical application of these platinum drugs are their inherent toxicities, as well as the high incidence of intrinsic and acquired drug resistance by tumors (Andrews and Howell, 1990; Galluzzi et al., 2012). Development of platinum drug resistance is also often associated with multidrug resistant phenotype in tumor cells. In particular for ovarian cancer, which is the leading cause of death from gynecologic malignancies, platinum drugs are used as standard first-line therapy (Mullany and Richards, 2012), with the initial response rate of up to 70% (Runowicz, 1992). However, 70% of those patients experience disease recurrence (Romero and Bast, 2012).
Resistance to platinum therapy, which is associated with incurable disease, eventually occurs in all patients treated for recurrent ovarian cancer, in addition to the approximately one-third of all women who are intrinsically resistant to cisplatin during primary treatment (Stewart et al., 2006). Platinum resistance is one of the most important factors in determining prognosis of ovarian cancer. Despite the extensive efforts that have been made to understand the complex mechanism underlying cellular resistance to platinum-based anticancer drugs, the nature of platinum drug resistance has not been clearly established (Wang and Lippard, 2005). To date, overcoming platinum drug resistance by pharmacological manipulation still represents a major clinical challenge. Therefore, there is a need in the art for strategies that can overcome cisplatin resistance and improve clinical outcomes.